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The hidden burden of Plasmodium vivax in India: sub microscopic parasites and asymptomatic infections complicate vivax elimination

Alex Eapen 1 ; Stuti Mohanty 2 ; Nabamita Bandyopadhyay 3 ; Rajashri Rani Oraon 2 ; Punam Barla 2 ; Sandhya Choubey 2 ; Syed Zeeshan Ali 2 ; Om P. Singh 3 ; K Pradhan 2 ; Neena Valecha 4 ; Jane Carlton 5 ; Harish C. Srivasatava 6 ; Ranvir Singh 6 ; S. K. Sharma 3 ; Nisha Desai 6 ; Ankita Patel 6 ; Samuel C. Wassmer 7 ; Nikunj Tandel 6 ; Anna Maria van Eijk 7 ; Patrick L. Sutton 7 ; Aswin Asokan 1 ; V. Sangeetha 1 ; Sangamithra Ravishankaran 1 ; Pavitra N. Rao 7 ; Steven A. Sullivan 7 ; Lalitha Ramanathapuram 7 ; Deena Kanagaraj 1 ; G Sri Lakshmi Priya 1
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Background: Malaria in India, while decreasing, remains a serious public health problem with nearly half of the global population at risk of Plasmodium vivax. The contribution of sub microscopic and asymptomatic infections to its persistence is poorly understood. Hence, it was planned to initiate a community study to determine the incidence and prevalence rate of complex malaria (mixed- species and mixed genotype infections) including asymptomatic malaria and a clinic study to investigate the impact of complex malaria on disease outcome in symptomatic individuals, while monitoring the population for continued and emerging drug resistance. Materials and Methods: We conducted the cross-sectional and clinic study in Chennai (Tamil Nadu, urban malaria), Nadiad (Gujarat, peri-urban malaria) and Raurkela (Odisha, peri-urban and rural malaria) during 2012-2015. Enrollment for community (quarterly) and clinic study (weekly) was carried out and all the malaria positive cases were followed on Days 2, 7, 14, 21, 28 and 42 in clinic study. Blood samples were used for microscopy and PCR. Ethical clearance and IRB approval was obtained from National Institute of Malaria Research of Indian Council of Medical Research and New Your University respectively. Results: Malaria prevalence was low (by PCR: 2.6% in Chennai, 7.0% in Nadiad, and 8.6% in Raurkela), with P. vivax dominating in Chennai and Nadiad (71% and 68% of infections, respectively), and P. falciparum in Raurkela (78%). The majority of infections detected in the Chennai surveys were sub microscopic (70.8%) and asymptomatic (70.8%), with lower values of 3.5% and 21.4% in Nadiad and 33.1% and 67.7% in Raurkela, respectively. In the clinic studies, prevalence by PCR was 21.1% (Chennai), 9.6% (Nadiad) and 5.0% (Raurkela), with a minority of infections sub microscopic (18.9%, 1.5% and 45.2%, respectively). Discussion: The study revealed that asymptomatic and sub microscopic burden of malaria in India is considerable, likely acting as a reservoir, which has implications for malaria elimination strategies.